dbacp08079
General Description
Peptide name : APETx4
Source/Organism : Anthopleura elegantissima
Linear/Cyclic : Linear
Chirality : L
Sequence Information
Sequence : GTTCYCGKTIGIYWFGKYSCPTNRGYTGSCPYFLGICCYPVD
Peptide length: 42
C-terminal modification: Linear
N-terminal modification : Free
Non-natural peptide information:
Activity Information
Assay type : CellTox Green Dye assay
Assay time : 20-h
Activity : Green object count = 300 /mm2 at 20 μM
Cell line : LNCaP
Cancer type : Prostate Cancer
Other activity : Anticancer
Physicochemical Properties
Amino acid composition bar chart :
Molecular mass : 4660.3299 Dalton
Aliphatic index : 0.440
Instability index : 14.1619
Hydrophobicity (GRAVY) : 0.0333
Isoelectric point : 8.293
Charge (pH 7) : 1.697
Aromaticity : 21.42
Molar extinction coefficient (cysteine, cystine): (6, 3)
Hydrophobic/hydrophilic ratio : 1.3333
hydrophobic moment : 0.4271
Missing amino acid : A,E,H,M,Q
Most occurring amino acid : G
Most occurring amino acid frequency : 7
Least occurring amino acid : W
Least occurring amino acid frequency : 1
Structural Information
3D structure :
Secondary structure fraction (Helix, Turn, Sheet): (7.1, 33., 45.)
SMILES Notation: CC[C@H](C)[C@H](NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CS)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CN)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)CC)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](Cc1ccccc1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CS)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)C(C)C)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O
Secondary Structure :
| Method | Prediction |
|---|---|
| GOR | TCEEETTTCCEEEEETTTTCTTCTTCCTCCCEEEEEECCCTC |
| Chou-Fasman (CF) | EEEECEEEEEEEEEECCCCCCCCEEEECCEEEEEEEEEECCC |
| Neural Network (NN) | CCEEECCCCCEEEEECCCCCCCCCCCCCCCCCCEEECCCCCC |
| Joint/Consensus | CCEEECCCCCEEEEECCCCCCCCCCCCCCCCEEEEEECCCCC |
Molecular Descriptors and ADMET Properties
Molecular Descriptors: Click here to download
ADMET Properties: Click here to download
Cross Referencing databases
CancerPPD : Not available
ApIAPDB : Not available
CancerPPD2 ID: 5576
Reference
1 : Moreels L, et al. APETx4, a Novel Sea Anemone Toxin and a Modulator of the Cancer-Relevant Potassium Channel K<sub>V</sub>10.1. Mar Drugs. 2017; 15:(unknown pages). doi: 10.3390/md15090287
Literature
Paper title : APETx4, a Novel Sea Anemone Toxin and a Modulator of the Cancer-Relevant Potassium Channel K<sub>V</sub>10.1.
Doi : https://doi.org/10.3390/md15090287
Abstract : The human ether-à-go-go channel (hEag1 or K<sub>V</sub>10.1) is a cancer-relevant voltage-gated potassium channel that is overexpressed in a majority of human tumors. Peptides that are able to selectively inhibit this channel can be lead compounds in the search for new anticancer drugs. Here, we report the activity-guided purification and electrophysiological characterization of a novel K<sub>V</sub>10.1 inhibitor from the sea anemone Anthopleura elegantissima. Purified sea anemone fractions were screened for inhibitory activity on K<sub>V</sub>10.1 by measuring whole-cell currents as expressed in Xenopus laevis oocytes using the two-microelectrode voltage clamp technique. Fractions that showed activity on Kv10.1 were further purified by RP-HPLC. The amino acid sequence of the peptide was determined by a combination of MALDI- LIFT-TOF/TOF MS/MS and CID-ESI-FT-ICR MS/MS and showed a high similarity with APETx1 and APETx3 and was therefore named APETx4. Subsequently, the peptide was electrophysiologically characterized on K<sub>V</sub>10.1. The selectivity of the toxin was investigated on an array of voltage-gated ion channels, including the cardiac human ether-à-go-go-related gene potassium channel (hERG or Kv11.1). The toxin inhibits K<sub>V</sub>10.1 with an IC<sub>50</sub> value of 1.1 μM. In the presence of a similar toxin concentration, a shift of the activation curve towards more positive potentials was observed. Similar to the effect of the gating modifier toxin APETx1 on hERG, the inhibition of Kv10.1 by the isolated toxin is reduced at more positive voltages and the peptide seems to keep the channel in a closed state. Although the peptide also induces inhibitory effects on other K<sub>V</sub> and Na<sub>V</sub> channels, it exhibits no significant effect on hERG. Moreover, APETx4 induces a concentration-dependent cytotoxic and proapoptotic effect in various cancerous and noncancerous cell lines. This newly identified K<sub>V</sub>10.1 inhibitor can be used as a tool to further characterize the oncogenic channel K<sub>V</sub>10.1 or as a scaffold for the design and synthesis of more potent and safer anticancer drugs.